Genetic contribution to asthma severity?

13/8/02. By the Public Health Genetics Unit

A study published in the Lancet suggests that variants of a gene encoding the protein interleukin 12B are associated with severity of disease in children who have asthma.

IL12B plays a role in immune responses to viruses and airborne allergens. The researchers typed a polymorphism in the IL12B gene in two separate groups, each containing about 400 children, from a population cohort of six-year-olds in Perth, Western Australia. The polymorphism is in the promoter region of the gene, a regulatory segment that affects the activity of the gene but does not change the protein that is produced.

Asthmatic children who had one copy of the gene containing a 4 base-pair insertion in the promoter region, and one copy of the gene without this insertion (heterozygotes), tended to have more severe asthma than children with either two gene copies containing the insertion or two copies containing the deletion (homozygotes). Biochemical studies showed that the heterozygotes produced less of the IL12B protein than did either group of homozygotes. There was no association between the IL12B polymorphism and susceptibility to asthma.

The symptoms of asthma range from mild to moderate to severe, and can be life-threatening.

PHGU comment: The fact that this finding was replicated in two separate groups of children from the cohort strengthens its claim to significance. IL12B is also a biologically plausible candidate for involvement in the severity of a disease that is known to be associated with immune system function. However, the fact that heterozygotes produced less IL12B than did either group of homozygotes is difficult to reconcile with current understanding of the regulation of gene expression.

Article courtesy of the Public Health Genetics Unit .

Further reading

Morahan G et al. Association of IL12B promoter polymorphism with severity of atopic and non-atopic asthma in children. Lancet 2002 360: 455-459. Abstract

Sandford A and Pare P (2002) Lancet 360: 422-423. Commentary